Monomethyl auristatin E and paclitaxel use different mechanisms to alter intracellular calcium signaling.

Network pharmacology and molecular docking-based strategy to determine the potential mechanism for escitalopram-mediated long QT syndrome.

Traditional Chinese medicines formula supplementation to late pregnancy sows enhance the ileal barrier and anti-inflammatory capacity of their offspring.

Behavioral and transcriptomic analyses reveal neurotoxicity and mechanism of action of DEHP in female pubertal mice with or without type 2 diabetes mellitus.

Bioactive components from Kaixin san alleviate bradyarrhythmia via modulation of the calcium signaling pathway: Integrated UPLC-Q-TOF/MS, network pharmacology, and experimental validation.

Calcium dysregulation in Alzheimer's disease: unraveling the molecular nexus of neuronal dysfunction and therapeutic opportunities.

Mini-review: "Hippocalcin: Molecular mechanisms and therapeutic potential in neuronal function".

Chitosan oligosaccharide regulates host defense in pepper plants against cucumber mosaic virus.

The dynamic duo: Calcium signaling and ultrasound modulation of cellular viscoelasticity: Comment on "Viscoelastic mechanics of living cells" by Zhou et al.

Dendrobium bigibbum Lindl. is one of the native species of orchids in the Philippines. Its pharmaceutical potentials have already been explored in Asian countries. Meanwhile, its seed is one of the major constraints for seed germination and mycorrhizal association with compatible basidiomycetes influences the germination of the seeds. In the formation of mycorrhizal association, calcium signaling is one of the initial responses of the plants wherein calcium serves as secondary messenger which triggers physiological functions and changes in the plants and the fungal symbionts as well. In this article, the molecular expression of calcium binding protein was determined in two stages of developments (rhizoid and seedling stage). In vitro cultivation of D. bigibbum with selected basidiomycetes were extracted. Quantitative Reverse Transcriptase - Polymerase Chain Reaction was used to determine the Cycle Threshold values. Results revealed the upregulation of the calcium binding proteins which indicates the elevation of calcium concentration, thus, there is a presence of plant-fungal interaction.

Design of a peripherally biased NPSR1 antagonist for neuropeptide S induced inflammation.

MicroRNA responses to alkaline stress and the key role of the miR156-MsSPL2/6B module in alfalfa.

Tissue-specific transcriptome analysis in Propsilocerus akamusi provides novel insights into the regulatory mechanisms under deltamethrin exposure.

The ecological risk of diamide insecticide cyclaniliprole to Daphnia magna: A multi-level comprehensive analysis.

BackgroundMitochondrial dysfunction and dysregulated calcium homeostasis contribute to Alzheimer’s disease (AD) pathogenesis. The extrasynaptic N-methyl-D-aspartic acid (NMDA) receptor (eNMDAR) plays a crucial role in calcium influx and subsequent signaling cascades. In individuals with AD, the reduced expression and function of glutamate transporter-1 (GLT-1) result in glutamate spillover from the synaptic clefts to the extrasynaptic region, thereby activating eNMDAR and inducing mitochondrial damage. Ceftriaxone (Cef) has been reported to ameliorate cognitive deficits in APPswe/PS1dE9 (APP/PS1) mice by upregulating GLT-1. This study aimed to explore whether Cef alleviates mitochondrial dysfunction to improve cognitive impairment and the roles of GLT-1 and eNMDAR, particularly the participation of eNMDAR-induced intracellular calcium signaling in this process.MethodsC57BL/6J, APP/PS1, and GLT-1-knockdown APP/PS1 mice were used. NMDA (1 mM, 2 µL per ventricle) was injected cerebroventricularly into APP/PS1 mice once to activate eNMDAR. Cef (200 mg/kg) was intraperitoneally administered for 14 days. Cognitive function was evaluated by novel object recognition, novel location recognition and Morris water maze tests. Hippocampal mitochondrial ultrastructure was observed using transmission electron microscopy. Hippocampal mitochondrial membrane potential (MMP) was detected using JC-1 staining. The expression of eNMDAR and proteins related to mitochondrial biogenesis and dynamics was evaluated by western blot. A neuron‒astrocyte coculture derived from the cerebral cortex of embryonic mice was used to evaluate the effects of Cef on eNMDAR-induced neuronal calcium influx, mitochondrial calcium accumulation and MMP loss using live-cell imaging.ResultsCef treatment attenuated hippocampal mitochondrial dysfunction, including ultrastructural damage, reduced aspect ratio, dysregulation of MMP, impaired biogenesis and dynamics, and cognitive deficits, and prevented the upregulation of eNMDAR expression in APP/PS1 mice in a GLT-1-dependent manner. These protective effects on hippocampal mitochondrial dysfunction and cognitive deficits were counteracted by eNMDAR activation. Furthermore, Cef incubation inhibited eNMDAR-mediated calcium influx in a GLT-1-dependent way and reduced MMP in primary cortical neurons. Notably, Cef incubation significantly suppressed mitochondrial calcium overload, which was mechanistically linked to the observed decline in MMP.ConclusionsCef treatment prevented the upregulation of eNMDAR expression and the subsequent extracellular calcium influx in a GLT-1-dependent manner, thereby reducing mitochondrial calcium loading and ultimately mitigating mitochondrial damage and cognitive deficits in APP/PS1 mice.Supplementary InformationThe online version contains supplementary material available at10.1186/s13195-025-01900-w.

Calcium blockers protect against sensory epithelial damage and hearing loss in Cx26-cKO mice.

Eldecalcitol ameliorates type 2 diabetic osteoporosis by attenuating endothelial ferroptosis via the SOCE/O-GlcNAcylation axis.

Over-excitation of tyrosine hydroxylase neurons in the paraventricular nucleus of the hypothalamus drives a neuroimmune positive feedback loop in rheumatoid arthritis.

Introduction Mutations in the DDX3X gene are the primary cause of DDX3X syndrome, with over 800 diagnosed families worldwide. DDX3X is also recognized as a single-gene driver for rare syndromes associated with epilepsy, autism, and developmental disorders. Clinical studies suggest potential links between DDX3X mutations and various cardiac comorbidities. However, there is no report on whether Ddx3xa knockout leads to cardiac phenotypes or whether a zebrafish ddx3xa gene knockout model has been used for such research. This study is based on the high genomic conservation between zebrafish and humans, utilizing a zebrafish model to investigate the potential links between DDX3X mutations and various cardiac comorbidities, as well as the underlying mechanisms. Methods A ddx3xa knockout model was constructed using CRISPR/Cas9 technology. To elucidate the molecular mechanisms, we performed transcriptome-wide profiling via RNA-Seq to identify differentially expressed genes and dysregulated signaling pathways. The spatiotemporal expression patterns of key genes were assessed using whole-mount in situ hybridization (WISH). Additionally, the critical role of Wnt/β-catenin signaling in the mutant phenotype was further validated using the Wnt inhibitor IWR-1. Results Homozygous knockout ( ddx3xa −/− ) embryos exhibited developmental delay, trunk malformations, and severe cardiac abnormalities, including pericardial edema, defective cardiac looping, and cardiac contractile dysfunction. Ribonucleic Acid Sequencing (RNA-seq) analysis of ddx3xa −/− zebrafish at 72 h post-fertilization (hpf) revealed significant enrichment in pathways related to actin cytoskeleton organization, calcium signaling, cardiac and vascular smooth muscle contraction, and Wnt signaling. Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (QRT-PCR) and in situ hybridization confirmed dysregulated expression of key cardiac development genes ( bmp4 , actn2b , tbx5 , nppb ) and significantly impaired cardiac function. Given the role of Wnt signaling in cardiogenesis, we further analyzed this pathway and found that ddx3xa knockout upregulated the key Wnt/β-catenin transcription factor Tcf/Lef1 (T Cell Factor/Lymphoid Enhancer Factor 1) and disrupted its target genes ( bmp4 , tbx5 ) expression. Crucially, treatment of 72 hpf mutant embryos with the Wnt inhibitor IWR-1 partially rescued both the cardiac malformations and the aberrant expression of its target genes. Discussion This study provides the first evidence that ddx3xa regulates cardiac morphogenesis by modulating the Wnt/β-catenin signaling pathway, offering direct experimental insight into the mechanisms underlying cardiac comorbidities in DDX3X syndrome. It also highlights the unique value of the zebrafish model for dissecting conserved pathogenic pathways and exploring targeted therapeutic strategies.

Abstract The neuron cell generates a nonhomogeneous environment composed of microstructures with varying influxes and outfluxes at different sites. However, there were no documented efforts to examine neuronal calcium (Ca2+) signaling pathway with nonhomogeneous buffering mechanisms and influences of localized influxes and outfluxes in three-dimensional contexts. Therefore, a three-dimensional framework has been proposed to examine neuronal Ca2+ signaling system regulating β-amyloid (Aβ) production and adenosine triphosphate (ATP) release. We considered that the properties of cellular mechanisms are non-uniform along x, y, and z axes. The present model incorporates several types of buffers, namely EGTA, S100B, Calbindin-D28K, Calmodulin, and several crucial mechanisms like Sarcoendoplasmic Reticulum Calcium ATPase (SERCA) pump, IP3-receptor (IP3R), voltage-gated calcium channel (VGCC), ryanodine-receptor (RyR), sodium-calcium exchanger (NCX), etc. The present three-dimensional model is more realistic as it represents the source influx processes along different planes and surfaces of the cell. The Finite Element method (FEM), along with the Crank-Nicholson (CN) procedure, was used to acquire the numerical results. Neurotoxic events that may contribute to disease-related diseases like Ischemia, Alzheimer's (AD), etc. may stem from imbalances in Ca2+ levels, Aβ production, and ATP release due to different cellular processes in neurons.